摘要:高遷移率族核小體結(jié)合蛋白(High-mobility group nucleosome-binding proteins,HMGN)幾乎存在于所有哺乳動(dòng)物和多數(shù)脊椎動(dòng)物的細(xì)胞核中,屬于HMG蛋白家族。HMGN是現(xiàn)在唯一已知的特異性結(jié)合在核小體上的非組蛋白,能夠改變?nèi)旧|(zhì)的結(jié)構(gòu)、增強(qiáng)染色質(zhì)模板的轉(zhuǎn)錄/復(fù)制,參與DNA復(fù)制/表達(dá)、細(xì)胞分化、器官發(fā)育及基因表達(dá)調(diào)控等細(xì)胞的生命活動(dòng)。目前,HMGN包括HMGN1、HMGN2、HMGN3、HMGN4和HMGN5。研究顯示,HMGN1據(jù)其所在位置的不同,有著截然不同的功能。在細(xì)胞核內(nèi),HMGN1作為一種特殊定位的生物蛋白,與核小體直接結(jié)合而調(diào)節(jié)基因的轉(zhuǎn)錄和影響染色質(zhì)的結(jié)構(gòu);在細(xì)胞外環(huán)境,HMGN1通過toll樣受體4(Toll-like receptor 4,TLR4)促進(jìn)抗原提呈細(xì)胞(Antigen-presenting cells,APCs)的活化和補(bǔ)充,從而促進(jìn)特定抗原免疫應(yīng)答。警報(bào)素(Alarmins)是一種內(nèi)源性介質(zhì),當(dāng)機(jī)體受到危險(xiǎn)信號(hào)刺激時(shí),它能快速的釋放到細(xì)胞外,招募并激活A(yù)PCs增強(qiáng)特異性免疫和非特異性免疫反應(yīng)。認(rèn)識(shí)HMGN及其作用對(duì)其在多方面的應(yīng)用有重要意義。
關(guān)鍵詞:高遷移率族核小體蛋白(HMGN);警報(bào)素;核小體;免疫
中圖分類號(hào):R39211
文獻(xiàn)標(biāo)識(shí)碼:A
文章編號(hào):1008-0457(2017)03-0068-07國際DOI編碼:10.15958/j.cnki.sdnyswxb.2017.03.012
Abstract:High-mobility group nucleosome-binding proteins are members of the high mobility group protein familyHMGN exists in the nucleus of the almost all mammals and most vertebratesHMGN are the only non-histone proteins known to specifically bind inside the nucleosomes,which can change chromatin structure,enhance transcription and replication of chromatin template,and participate in DNA replication and expression,cell differentiation,organ development and gene expression regulation and other cell life activitiesHMGN protein family is composed of five proteins,HMGN1 through 5Previous studies indicated that HMGN1 has two distinct functions depending on its positionIn nucleus,HMGN1 acts as a location-specific biological protein,and can regulate gene transcription and influence chromatin structure by directly binding to nucleosomesHo-wever,extracellular HMGN1 promotes antigen-specific immune responses by promoting the activation and recruitment of antigen-presenting cells(APCs)through toll-like receptor 4(TLR4)Alarmins,as endogenous mediators,could be rapidly released from cells in response to dangerous signalsAlarmin then recruits and activates APCs to enhance innate and adaptive immune responsesHMGN1 is a recently identified alarminHere,we introduce the HMGN and its potential role in medical and other possible fields
Key words:highmobility group nucleosome-binding protein 1(HMGN1);alarmins;nucleosome;immunity
HMG蛋白的首次發(fā)現(xiàn)是在1973年,Johns EW與同事Goodwin GH和Sanders C從小牛胸腺細(xì)胞中通過035-M-NaCl提取分離得到兩組蛋白質(zhì)[1,2],一組蛋白易溶于10%的三氯乙酸,因在聚丙烯酰胺凝膠電泳中遷移快速,將其稱為“高遷移率族”蛋白,即HMG蛋白;另一組蛋白質(zhì)在聚丙烯酰胺凝膠電泳中遷移較慢,將其稱為“低遷移率族”蛋白[1]。隨后,實(shí)驗(yàn)通過凝膠過濾部分分離HMG蛋白發(fā)現(xiàn),HMG蛋白中至少含有兩種蛋白,命名為蛋白1(HMG-1)和蛋白2(HMG-2),這兩種蛋白質(zhì)的酸/堿性氨基酸都超過55%,每個(gè)細(xì)胞核中約105分子的HMG-1和2[1,2]。……